Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

Expression Profiles of Protease in Onychomycosis-Related Pathogenic Trichophyton rubrum and Tinea Capitis-Related Pathogenic Trichophyton violaceum.

The two fungal species Trichophyton rubrum and Trichophyton violaceum are common pathogens on human, infecting keratinized tissue of the outer body parts. Both species are belonging to the "Trichophyton rubrum complex" and share very high similarity in the genome. Secreted proteinases, key factors for keratin degradation, are nearly identical. Contrary, the ecological niches are differing. Trichophyton rubrum preferably infects skin and nails, whereas T. violaceum preferably infects the scalp. We postulate, that differences in the protease expression contribute to differences in ecological preferences. We analyzed the expression profiles of all 22 endoprotease genes, 12 subtilisins (S8A), 5 deuterolysins (M35) and 5 fungalysins (M36), for both species. To compare the influence of the keratin source, we designed experiments with human nail keratin, sheep wool keratin and keratin free cultivation media. Samples were taken at 12 h, 24 h, 48 h and 96 h post incubation in keratin medium. The expression of the proteases is higher in wool-keratin medium compared to human nail medium, with the exception of MEP4 and SUB6. Expression in the keratin-free medium is lowest. The expression profiles of the two species are remarkable different. The expression of MEP1, MEP3, SUB5, SUB11 and SUB12 are higher in T. rubrum compared to T. violaceum. MEP2, NpIIc, NpIIe, SUB1, SUB3, SUB4, SUB7 and SUB8 are higher expressed in T. violaceum compared to T. rubrum. The differences of the protease expression in the two species may expalin the differences in the ecological niches. Further analysis are necessary to verify the hypothesis.Please check and conform the edit made in title.Here I thinke the species of strains shouldnt be capital， and the right expression should be,  "Expression Profiles of Protease in Onychomycosis-Related Pathogenic Trichophyton rubrum and Tinea Capitis-Related Pathogenic Trichophyton violaceum"Author names: Please confirm if the author names are presented accurately and in the correct se-quence (given name, middle name/initial, family name). Author 1 Given name: [Jingjing] Last name [Chen], Author 2 Given name: [Yangmin] Last name [Gao], Author 3 Given name: [Shuzhen] Last name [Xiong], Author 4 Given name: [Ping] Last name [Zhan]. Also, kindly confirm the details in the metadata are correct.YesPlease check and confirm the inserted city and country are correctly identified for affiliation 3.Please change the affiliations, Affiliation 2: ²Jiangxi Provincial Clinical Research Center for Skin Diseases, Dermatology Hospital of Jiangxi Province,The Affiliated Dermatology Hospital of Nanchang University, Nanchang, 330200, Jiangxi; Affiliation 3: 3Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College,Nanchang 330001, Jiangxi. Thanks a lot!

Genetic diagnosis of a rare COL7A1 variant causing dystrophic epidermolysis bullosa pruriginosa through whole­exome sequencing.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of inherited DEB. In the present study, whole-exome sequencing was conducted on 12 individuals from the same affected family and a rare heterozygous variation was identified in the collagen type VII, α1 (COL7A1) gene, namely c.6859G>A (p.Gly2287Arg). Subsequently, this heterozygous variant was confirmed using Sanger sequencing of individual plasma cell-free DNA (cfDNA) and it was demonstrated for the first time, to the best of our knowledge, that COL7A1 exons can be amplified from plasma cfDNA. Within the large pedigree examined, 14 out of 18 individuals carried the variant, 3 carried the wild type, and one exceptional case, III-9, showed no disease symptoms despite carrying the disease variant. A general association between genotype and phenotype was established. Of note, the mutation landscape indicated that this G2287R variant is primarily reported in Asian countries. In silico structure prediction suggested that the residue resulting from the mutation may affect collagen protein stability. In conclusion, the present study provides evidence for the involvement of the COL7A1 G2287R gene variant in the development of DEB-Pr and highlights the potential utility of cfDNA in genetic disease diagnosis.

Case report: Mucous membrane pemphigoid with complicated autoantibody profile indicating the necessity of comprehensive diagnostic methods and the contribution of IgA autoantibodies.

Mucous membrane pemphigoid (MMP) is a type of subepithelial autoimmune bullous disease, affecting various mucosae, occasionally with skin lesions. Both diagnosis and treatment of MMP are difficult. Although multiple autoantigens have been identified for MMP, the pathogenesis of MMP is still unclear. In this study, we presented a female MMP case with extensive oral mucosal lesions and skin lesions, particularly on the extremities. IgG and IgA autoantibodies against multiple autoantigens including BP180, laminin 332, integrinα6ß4 and desmoglein 3, and IgM autoantibodies against BP180 were identified during the disease course. Compared with IgG autoantibodies, the levels of IgA autoantibodies against various autoantigens decreased more significantly with improvement of clinical features after the initiation of treatments. Our findings indicated the importance of comprehensive autoantibody screening for different immunoglobulin types and autoantigens at multiple time points for the precise diagnosis of various autoimmune bullous diseases, and the significant involvement of IgA autoantibodies into the pathogenesis of MMP.

Potential contribution of anti-p200 autoantibodies to mucosal lesions in anti-p200 pemphigoid.

Anti-p200 pemphigoid is a relatively rare subepidermal autoimmune bullous disease (AIBD), which was firstly reported by Detlef Zillikens, Takashi Hashimoto and others in 1996. Skin lesions are considered as the major clinical features of this disease, with occasional involvement of mucosal lesions. The mechanism of mucosal lesions involved in anti-p200 pemphigoid is still unclear. In the present study, we aimed to analyze published data on cases and case series of anti-p200 pemphigoid with mucosal lesions and explored the potential contribution of anti-p200 autoantibodies to mucosal lesions. A total of 32 papers that comprised 52 anti-p200 pemphigoid patients with various mucosal lesions were included in this review. Oral lesions were involved in 75.0% patients, followed by genital lesions (26.9%) and ocular lesions (11.54%). Only one patient had psoriasis, 26.9% patients had multiple mucosal lesions, and 30.8% cases had comorbidity of other AIBDs, particularly anti-laminin (LM) 332-type mucous membrane pemphigoid (MMP). In comparison with anti-LM332-type MMP, anti-BP180-type MMP and epidermolysis bullosa acquisita, higher frequency of genital lesions was identified as a unique character of anti-p200 pemphigoid with mucosal lesions. These results indicated that anti-p200 autoantibodies might contribute to mucosal lesions in a pattern different from other MMP-related autoantibodies, although its pathogenetic mechanisms are still unclear.

Case Report: Variety of Target Antigens During 1 Year Follow-Up of a Patient Initially Diagnosed With Bullous Pemphigoid.

Autoimmune bullous diseases (AIBDs), presenting cutaneous and/or mucosal bullous lesions, are classified into pemphigus and pemphigoid diseases. A longtime observation for complicated AIBD cases is rarely reported. In this study, serum samples of one AIBD patient were collected at seven different time points during the disease course including a relapse, which were examined by our conventional and newly developed methods for the detection of autoantibodies. Interestingly, we found changes of both the presence and the titers of various autoantibodies in accordance with the changes of clinical features during the whole disease course, which indicated that the patient started as bullous pemphigoid and relapsed as concurrence of bullous pemphigoid and mucosal-dominant-type pemphigus vulgaris.

Molecular epidemiology and in vitro antifungal susceptibility of Trichophyton schoenleinii, agent of tinea capitis favosa.

Trichophyton schoenleinii is an anthropophilic dermatophyte usually causing tinea favosa. Only few studies have provided data on molecular epidemiology and antifungal profiles of this fungus due to its limited prevalence after 1950s. Forty-nine strains from Asia (n = 27), Africa (n = 10), Europe (n = 10) and from unknown regions (n = 2) were analysed with amplified fragment length polymorphism fingerprinting (AFLP) to reveal intraspecific genetic diversity in this dataset. Amplified fragment length polymorphism fingerprinting genotyping revealed five clusters which did not correspond to geographic origins or clinical characteristics. Additionally, in vitro antifungal susceptibility to seven antifungals was provided for all strains. Terbinafine, ketoconazole, miconazole and itraconazole proved to be the most effective drugs, followed by griseofulvin. No correlation between genotypes and differences in antifungal susceptibility was observed. It is concluded that the AFLP groups are lineages within a single species.

Prevalence and antifungal susceptibility of Sporothrix species in Jiangxi, central China.

Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation of pathogenic Sporothrix species. Until recently, Sporothrix globosa was considered as the unique Chinese species causing this disorder. In the present study, 33 clinical Sporothrix strains isolated from Jiangxi, China, were classified and antifungal susceptibility for each strain was determined. Thirteen S. globosa strains and 20 S. schenckii strains were identified by morphology and by multilocus analysis using rDNA ITS, CAL, and EF1α (i.e., internal transcribed spacer, calmodulin and elongation factor-1α). In vitro antifungal susceptibility testing of yeast phases indicated that itraconazole, terbinafine, and posaconazole were most effective against both species, followed by amphotericin B and voriconazole, while fluconazole, 5-fluorocytosine had low efficacy with high MICs. Co-occurrence of S. schenckii and S. globosa in central China may indicate different routes of transmission in this area.

Progressive silencing of the zinc transporter Zip8 (Slc39a8) in chronic cadmium-exposed lung epithelial cells.

Cadmium (Cd), a non-essential metal, stealthily enters the cells by utilizing the essential metal importing pathways. The zinc transporters Zip8, Zip14, and divalent metal transporter 1 (Dmt1) are now emerging as several important metal transporters involved in cellular Cd incorporation and their expressions have been shown to be down-regulated in several Cd-resistant (CdR) cell lines, however, the involvement of these transporters during the development of Cd-resistance in lung cells is unclear. In this study, we therefore check the expression of these metal transporters in our previously established rat lung epithelial cells (LECs) and show that the level of Zip8 is progressively silenced when LECs are adapted to increasing concentrations of CdCl2 (from 1 to 20 µM). Subsequent measurement of the cellular Cd content indicated that CdR LECs exhibit a marked decrease of Cd accumulation, possibly due to the loss of Zip8 expression. We investigate the possibility that epigenetic silencing of the Zip8 gene by DNA hypermethylation is involved in the down-regulation of Zip8 expression. CdR LECs show a higher mRNA level of DNA methyltransferase 3b (Dnmt3b) than parental cells. Treatment of CdR LECs with 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferases, reverted the expression of Zip8 and sensitivity to Cd in these cells, indicating the critical role of Zip8 for Cd import. Taken together, our results demonstrate that the progressive silencing of Zip8 expression is involved in the acquisition of resistance against Cd in lung cells, representing an adaptive survival mechanism that resists Cd-induced cytotoxicity.

Aberrant cytokine secretion and zinc uptake in chronic cadmium-exposed lung epithelial cells.

PURPOSE: Our previous results showed that cadmium (Cd)-adapted lung epithelial cells (LECs) developed resistance to apoptosis due to non-responsiveness of the c-Jun N-terminal kinase pathway and augmented expression of cytokeratin 8. Since cellular Cd entry is a prerequisite in order for Cd to elicit its cytotoxicity, therefore, we wonder if there are differential metal ion transport ability and also other phenotypic changes that occurred in these Cd-resistant LECs. EXPERIMENTAL DESIGN AND RESULTS: Here, we explored further and found that the zinc (Zn) importer Zip8 was stably abolished in these cells along with a marked decrease of Cd and Zn accumulation. Moreover, by cell migration assays and cytokine antibody array analysis, we found that Cd-adapted cells exhibit enhanced migratory ability possibly due to elevated secretions of vascular endothelial growth factor and macrophage inflammatory protein-3 alpha (MIP-3α). CONCLUSION AND CLINICAL RELEVANCE: Taken together, our results show that during chronic Cd exposure, lung cells antagonize excessive cellular Cd-influx by abolishing Zip8 expression to reduce Cd-toxicity; however, this also renders cells with a diminished Zn uptake. The imbalance of Zn homeostasis and elevation of angiogenic and epithelial-mesenchymal transition-promoting cytokines in Cd-adapted cells might thus likely promote Zn deficiency, angiogenesis, and cell invasion.